Antiviral defense: interferons and beyond

Abstract

Mice lacking the adaptor protein that initiates an antiviral response downstream of the RNA helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) have recently been described. These studies highlight the essential and nonredundant role of nucleic acid recognition in the induction of type I interferon production and raise important questions regarding the nature of cell-autonomous virus detection in coordinating the antiviral response.

Figure 1.

Control of antiviral defense by IPS-1. (A) In normal cells infected with an RNA virus, IPS-1–dependent signaling activates type I IFNs, which turn on IFN-inducible genes in both infected cells and neighboring, uninfected cells. IPS-1 might also control cell-intrinsic apoptosis and the induction of ligands for NK cells and CTLs, but only in infected cells. (B) In IPS-1–deficient cells, all four functions depicted in part A are lost and antiviral defenses are fully compromised. (C) Treatment of IPS-1–deficient cells with type I IFNs (either TLR-activated systemic IFNs or exogenous type I IFNs) only restores the IPS-1–independent response mediated by IFN-inducible genes.